The objective of this Phase I SBIR proposal is the development of an imaging system for real-time identification of residual tumor margins during surgery. The main purpose of breast conservation surgery is to remove the entire tumor and obtain clear margins (a zone devoid of tumor) around the cavity to decrease the chance of local tumor recurrence. However there are challenges identifying the residual tumor at the margin. Because of this, inadequate margins are found at the first operation in 20-55% of breast cancers removed by open lumpectomy. In addition, 75-90% of recurrences occur at the site of the original lumpectomy. This proposal will use near-infrared absorbing nanoparticles as an agent for the identification of residual tumor cells during surgery. In a technique similar to current narrowband imaging, which utilizes visible wavelengths, our near-infrared narrowband imaging (NIRNBI) system utilizes nanoparticles that strongly absorb near-infrared wavelengths as agents to identify the tumor cells. The NIRNBI system will operate in real-time, allowing the surgeon to visually identify areas where tumor cells are present in the wound bed. The surgeon can then resect the identified areas to obtain clear margins, and then re-image the field as confirmation (or continue to resect any newly identified areas). The specific aims of this proposal are: (i) Manufacture near-infrared absorbing nanoparticies for active targeting (systemic and topical use);(ii) Modify the existing prototype Near-Infrared Narrowband Imaging (NIRNBI) system for more rapid data capture and output;(iii) Evaluate the depth of imaging sensitivity in breast tissue mimicking phantoms to establish a 3-D sensitivity of the system;and (iv) Test the system in vivo using subcutaneous breast cancer tumors in an animal model.